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Osimertinib and Locally Ablative Radiotherapy in Patients With Synchronous Oligo-metastatic EGFR Mutant NSCLC (STEREO) (STEREO)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04908956
Recruitment Status : Recruiting
First Posted : June 1, 2021
Last Update Posted : April 7, 2022
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
European Thoracic Oncology Platform

Brief Summary:
STEREO is single-arm phase II study, which aims to evaluate the safety and efficacy of osimertinib combined with early locally ablative radiotherapy of all cancer sites in patients with synchronous oligo-metastatic (primary tumour and maximum 5 metastases) EGFR-mutant (exon 19 deletion or exon 21 L858R) NSCLC. Eradication of all macroscopic cancer sites at the time of primary diagnosis by combined modality treatment is expected to decrease the risk of resistance development with only microscopic disease potentially remaining. This will result in an improvement of PFS and OS without added high-grade toxicity.

Condition or disease Intervention/treatment Phase
NSCLC Stage IV EGFR Gene Mutation Drug: Osimertinib Radiation: Stereotactic Body Radiation Therapy (SBRT) Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicentre Single-arm Phase II Trial Assessing the Safety and Efficacy of First-line Osimertinib and Locally Ablative Radiotherapy in Patients With Synchronous Oligo-metastatic EGFR-mutant Non-small Cell Lung Cancer
Actual Study Start Date : December 31, 2021
Estimated Primary Completion Date : March 2026
Estimated Study Completion Date : March 2026

Resource links provided by the National Library of Medicine

Drug Information available for: Osimertinib

Arm Intervention/treatment
Experimental: Osimertinib & SBRT
Osimertinib 80mg once daily p.o., until progression or unacceptable toxicity & locally ablative radiotherapy (SBRT) to the primary tumour and to all metastatic sites.
Drug: Osimertinib

Osimertinib is a Tyrosine Kinase Inhibitor (TKI). It is an irreversible inhibitor of Epidermal Growth Factor Receptors (EGFRs) harboring sensitising-mutations (EGFRm) and TKI-resistance mutation T790M.

The appropriate number of osimertinib tablets (80 mg or 40 mg if the dose is reduced due to toxicity) will be provided to patients to be self-administered at home.

Other Name: Tagrisso

Radiation: Stereotactic Body Radiation Therapy (SBRT)
SBRT will be delivered using risk-adapted SBRT with a maximum of 5 SBRT fractions.




Primary Outcome Measures :
  1. Safety of first-line EGFR-targeting osimertinib and SBRT to the primary tumour and all metastases [ Time Frame: Rate of grade ≥2 pneumonitis, requiring medical treatment, any time during the first 18 months on trial follow-up ]
    Defined as the number of patients experiencing grade ≥2 pneumonitis, requiring medical treatment, any time during the first 18 months post enrolment over the total number of patients in the primary-endpoint safety cohort.

  2. Efficacy of first-line EGFR-targeting osimertinib and SBRT to the primary tumour and all metastases [ Time Frame: Time from the date of enrolment until documented progression or death, if progression is not documented, assessed for a maximum of approx. 44 months after enrolment of the first patient ]

    If safety is proven, efficacy will be hierarchically tested in terms of Progression-free survival (PFS) according to RECIST v1.1, in the efficacy cohort.

    PFS is defined as the time from the date of enrolment until documented progression or death, if progression is not documented.



Secondary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: Time from the date of enrolment until death from any cause. Censoring will occur at the last follow-up date, assessed for a maximum of approx. 44 months after enrolment of the first patient ]
    Defined as the time from the date of enrolment until death from any cause.

  2. Pattern of disease progression [ Time Frame: Evaluated up to 18-months post enrolment ]
    Defined as the pattern of disease progression is defined as the site of first progression: None, locoregional, distant (bone, brain, liver, etc.) or both locoregional and distant

  3. Distant progression-free survival [ Time Frame: Time from date of enrolment until development of new metastases, excluding oligo-metastases diagnosed at enrolment - assessed for a maximum of approx. 44 months after enrolment of the first patient ]
    Defined as the time from date of enrolment until development of new metastases, excluding oligo-metastases diagnosed at enrolment

  4. Objective response rate [ Time Frame: Time from enrolment across all trial assessment time-points - assessed for a maximum of approx. 44 months after enrolment of the first patient ]
    Defined as the percentage of patients that achieve a best overall response [complete response (CR) or partial response (PR)] according to RECIST v1.1

  5. Duration of response [ Time Frame: From the date of first documentation of objective response to the date of first documented progression, relapse or death- assessed for a maximum of approx. 44 months after enrolment of the first patient ]
    Defined as the interval from the date of first documentation of objective response (CR or PR, according to RECIST v1.1) to the date of first documented progression, relapse or death

  6. Adverse events according to CTCAE v5.0 [ Time Frame: Assessed for a maximum of approx. 44 months after enrolment of the first patient ]
    To assess the safety and tolerability of the treatment.

  7. Symptom-specific and global quality of life [ Time Frame: Assessed from baseline to 24 weeks on treatment ]
    QoL will be assessed by the Lung Cancer Symptom Scale, a 9-item questionnaire including six symptoms (i.e., appetite loss, fatigue, cough, dyspnoea, haemoptysis and pain) and three items addressing symptomatic distress, normal activity, and global QoL. The primary QoL endpoints will be the change in the LCSS total score (average of all 9 items) from baseline to 24 weeks on treatment.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed, treatment naïve EGFR-mutant NSCLC, with or without T790M resistance mutation. Presence of the sensitising EGFR-mutation (exon 19 deletion and/or exon 21 L858R) detected by an accredited laboratory.
  • Synchronous oligo-metastatic stage IV disease (max 5 lesions)
  • Measurable disease as defined according to RECIST v1.1
  • All lesions amenable for radical radiotherapy according to local judgment
  • Age ≥18 years
  • ECOG performance status 0-2
  • Life expectancy ≥12 months
  • Adequate haematological, renal & liver function
  • Women of childbearing potential, including women who had their last menstruation in the last 2 years, must have a negative urinary or serum pregnancy test within 7 days before enrolment.
  • Written IC for protocol treatment

Exclusion Criteria:

  • Prior chemotherapy, immunotherapy, radiotherapy or therapeutical surgery for NSCLC (an exception is the resection and postoperative radiotherapy of the resection cavity of CNS or adrenal metastases)
  • More than 5 distant oligo-metastases (any second intra-thoracic lesion will count as a distant metastasis; regional nodal metastases will not count towards 5 oligo-metastases) and more than 2 intra-thoracic lesions.
  • Brain metastases not amenable for radiosurgery or neurosurgery
  • Presence of leptomeningeal metastases
  • Symptomatic spinal cord compression
  • Extracranial metastatic locations not amenable for radical radiotherapy
  • Currently receiving medications or herbal supplements known to be potent CYP3A4 inducers
  • Any evidence of severe or uncontrolled systemic diseases
  • Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of osimertinib
  • Any of the following cardiac criteria: QTcF >470 msec; Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG; Any factors that increase the risk of QTc prolongation or risk of arrhythmic events
  • Past medical history of Interstitial Lung Disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD
  • Idiopathic pulmonary fibrosis which is a contraindication to lung radiation.
  • History of hypersensitivity to active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib.
  • Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements
  • Women who are pregnant or in the period of lactation.
  • Sexually active men and women of childbearing potential who are not willing to use an effective contraceptive method during the trial and up to 6 weeks for women and up to 4 months for men, after the last osimertinib dose.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04908956


Contacts
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Contact: Barbara Ruepp, PharmD +41315119400 barbara.ruepp@ibcsg.org

Locations
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Italy
SS Antonio e Biagio e Cesare Arrigo di Alessandria Not yet recruiting
Alessandria, Italy
Principal Investigator: Federica Grosso, MD         
IRCCS - Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) Not yet recruiting
Meldola, Italy, 47014
Principal Investigator: Angelo Delmonte, MD         
Instituto Europeo di Oncologia (IEO) Not yet recruiting
Milano, Italy
Principal Investigator: Filippo de Marinis, MD         
AULSS2 Marca Trevigiana Treviso Not yet recruiting
Treviso, Italy
Principal Investigator: Adolfo Favaretto, MD         
Korea, Republic of
National Cancer Center Not yet recruiting
Goyang-si, Korea, Republic of, 10408
Principal Investigator: Ji-Youn Han         
Severance Hospital, Yonsei University Health System Not yet recruiting
Sinchon-dong, Korea, Republic of
Principal Investigator: Byoung Chul Cho, MD         
Netherlands
The Netherlands Cancer Institute Amsterdam Not yet recruiting
Amsterdam, Netherlands, 1006 BE
Principal Investigator: Egbert Smit, MD         
Erasmus MC Not yet recruiting
Rotterdam, Netherlands
Principal Investigator: Anne-Marie Dingemans, MD         
Singapore
National University Hospital Not yet recruiting
Singapore, Singapore
Principal Investigator: Ross Soo, MD         
Spain
Hospital General de Alicante Not yet recruiting
Alicante, Spain, 03010
Principal Investigator: Bartomeu Massutí, MD         
Vall d'Hebron University Hospital Not yet recruiting
Barcelona, Spain, 08035
Principal Investigator: Nuria Pardo, MD         
Catalan Institute of Oncology Not yet recruiting
L'Hospitalet de Llobregat, Spain
Principal Investigator: Ernest Nadal, MD         
Centro Integral Oncologíco Clara Campal (CIOCC) HM Hospitales Not yet recruiting
Madrid, Spain, 28050
Principal Investigator: Miriam Dorta, MD         
Hospital Regional Universitario Málaga Not yet recruiting
Malaga, Spain, 29001
Principal Investigator: Manuel Cobo, MD         
Sweden
Karolinska Universitetssjukhuset Solna Not yet recruiting
Stockholm, Sweden, 171 76
Principal Investigator: Rolf Lewensohn, MD         
Switzerland
Universitätsspital Zürich USZ Recruiting
Zürich, Switzerland, 8091
Principal Investigator: Matthias Guckenberger, MD-PhD         
Sponsors and Collaborators
European Thoracic Oncology Platform
AstraZeneca
Investigators
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Study Chair: Matthias Guckenberger, MD-PhD University Hospital, Zürich
Publications:
Wang X, Zeng M. First-line tyrosine kinase inhibitor with or without aggressive upfront local radiation therapy in patients with EGFRm oligometastatic non-small cell lung cancer: Interim results of a randomized phase III, open-label clinical trial (SINDAS) (NCT02893332). Journal of Clinical Oncology 2020; 38(15_suppl): 9508-

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Responsible Party: European Thoracic Oncology Platform
ClinicalTrials.gov Identifier: NCT04908956    
Other Study ID Numbers: ETOP 17-20
2020-004114-35 ( EudraCT Number )
ESR-19-20384 ( Other Identifier: AstraZeneca )
First Posted: June 1, 2021    Key Record Dates
Last Update Posted: April 7, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by European Thoracic Oncology Platform:
NSCLC
EGFR mutation (exon 19 deletion and/or exon 21 L858R)
Osimertinib
SBRT
Additional relevant MeSH terms:
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Osimertinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action